Objective
The objective is to define the role of T cells and related soluble products (called cytokines) in the pathogenesis of Multiple Sclerosis (MS). It is widely believed that the understanding of the function of these cells may help in clarifying their role and may further help the understanding of the pathogenesis of MS. Finally these studies may define new therapeutic targets to treat MS. It has to be stressed that the results obtained in this project might provide further insight to understand the pathogenesis of other chronic autoimmune inflammatory processes.
Changes in the frequency and repertoire of MBP-specific T cells seems to be a common phenomenon in MS patients. The causes (epitope spreading, cross-reactive responses) and the effects of these modifications in the context of MS pathogenesis remain to be further investigated. For instance in some cases the pathogenic epitopes might have the characteristic of crypticity. Studies are also undergoing in order to define how professional APC could "trick" self-reactive T cells by inducing anergy or apoptosis. The TCRV-beta usage was determined in a group of well-characterised MS patients, and reported that a preferential expansion of certain TCRV-beta+ T cells, with an oligoclonal profile, was observed in MS patients. These patients are now longitudinally monitored. The unique TCR structure of autoantigen specific T cells might represent the ideal target for immunospecific therapies. The type of soluble product "cytokines", released by T cells, define the function of T lymphocytes. The preliminary results indicate that specific pattern of cytokine release were observed. Introducing the combinatory approach of in-situ detection for IFN-gamma mRNA, a cytokine that has negative effects on the evolution of MS. The results have indicated that T cells are highly activated in MS, but more importantly that a significant proportion of CD8+ T cells produce IFN-gamma in vivo, further stressing the possible role of this T cell sub-population in MS. Among the several adversary effects of gamma-IFN it has been shown that this cytokine to selectively allow Ca++ influx in T cells of MS patients. Cytokine may also be expressed as surface molecules and influence the inflammatory cells by direct contact. The modification of the expression and the role of enzymes such as metallo-proteinases is currently under study. A major effect has also been directed towards the study of another sub-population of T cells the "gamma-delta" and in particular on gamma-delta-T cells which also express NK markers. MS monozygotic, disease discordant twins represent the ideal population to study.To gain a unique position a major effort has been pursued in organising the largest database of identical twins in Italy. This database will provide the biggest reservoir to study monozygous discordant twins of the whole Europe. Finally we have established a novel and reliable animal model, which will allow us to test the potential of novel therapeutic approaches derived from these studies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences computer and information sciences databases
- medical and health sciences basic medicine neurology multiple sclerosis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
2288 GJ Rijswijk
Netherlands
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